Currently tumour is the most serious public health problem mankind is facing, and recently itcauses millions of deaths worldwide each year. Developing anti-tumor drugs with high efficacies and low toxicitities is the key to tumor therapy. At present, the focus of the research and development of anti-tumour drugs has shifted from cytotoxic drugs to targeted therapy drug. The success in marketing imatinibmakes people see the hope for curing tumor, thereby small molecular targeted drug development has entered a vigorous period and various inhibitors of tumour-associated signaling pathways enter the market and achieved great success.
Previous studies have found that aberrant activation of PI3K/Akt signaling pathway, in which Akt phosphorylation and then activation is a key step, is present in a variety of tumors. Simultaneous activation of the T308 and S473 sites of Akt is necessary for Akt activation. The development of PI3K/Akt signaling pathway inhibitors has become a hot spot in the research and development of antitumour drugs. There are dozens of this typeof drugs in clinical trials so far, and MK2206 and Triciribine are two typicaldrugs of such kind with significant clinical efficacies, and have a very good prospect for further development. Since the PI3K/Akt signaling pathway aberrant activation exists prevalently in tumors, the successful development of such drugs will achieve good social and economic benefits.
Benzimidazolone is an oxidized derivative of the carbon atom at the 2-position of imidazole ring, and has been widely used as an intermediate in dye industry (Jolanta S.et al. Dyes and pigments. 2001, 15-27). In addition, the benzimidazole derivatives also are widely used clinically because they possess significant pharmacological activity. For example, oxatomide, a second-generation anti-histamine drug, belongs to benzimidazole derivatives (Iwamoto K., et al. Arzneimittel-forschung-drug Research. 2001, 51: 971-976). In a Chinese patent application CN201110326737.9, the applicants introduce methylacryloyl group on nirogen at 3-position of benzimidazolone, resulting methylacryloyl-benzimidazolone (methylacryloyl-benzimidazole (thio) ketone) derivatives that show a extremely high antibacterial activity. Also in this patent application a method for preparing such compounds has been disclosed, and concrete chemical structures are presented.